Micro-environment causes reversible changes in DNA methylation and mRNA expression profiles in patient-derived glioma stem cells. PLoS One 2014;9(4):e94045
Date
04/15/2014Pubmed ID
24728236Pubmed Central ID
PMC3984100DOI
10.1371/journal.pone.0094045Scopus ID
2-s2.0-84899653917 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient's tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing.
Author List
Baysan M, Woolard K, Bozdag S, Riddick G, Kotliarova S, Cam MC, Belova GI, Ahn S, Zhang W, Song H, Walling J, Stevenson H, Meltzer P, Fine HAMESH terms used to index this publication - Major topics in bold
AnimalsDNA Methylation
Female
Glioma
Humans
In Vitro Techniques
Mice
Mice, SCID
Neoplastic Stem Cells
Polymorphism, Single Nucleotide
Principal Component Analysis
Prospective Studies
Tumor Cells, Cultured
